Pigment dispersion syndrome is an important cause of secondary glaucoma in humans, its pathogenesis is obscure, and therapeutic measures are satisfactory at best. A new mouse model that bears a distant, but interesting, resemblance to the human disease has been described in DBA/2J mice. In this model, as pigment dispersion escalates leaving iris atrophy in its wake, elevated intraocular pressure ensues, leading to optic nerve atrophy and vision impairment. One of the two mutant genes that give rise to the disease is expressed, surprisingly, in dendritic cells of bone marrow origin, implying a possible role for inflammation/immunity in the pathogenesis. The phenotype resulting from mutation of this gene involves pigment dispersion, slit-like radial trans-illumination defects and deterioration of the iris pigment epithelium. Recent experiments have determined that aqueous humor from eyes of affected DBA/2 J mice lacks the capacity to suppress T cell activation, an abnormality that actually precedes the onset of clinical evidence of pigment dispersion, and evidence of inflammation is already present at 4 months of age, implying a pathogenic role for inflammation in the disease. Moreover, DBA/2J eyes destined to develop glaucoma lack the capacity to promote anterior chamber associated immune deviation and they display impaired ocular immune privilege. Based on these findings, and the knowledge that degeneration of pigment epithelial cells of iris and ciliary body is an important manifestation of the disease, we have developed an experimental plan that links abnormalities in the ability of the DBA/2J eye to regulate inflammation and immune responses to the pathogenesis of pigment dispersion and iris atrophy. We hypothesize that ocular immune abnormalities in DBA/2J mice predispose to the development of autoimmunity directed at melanin-associated antigens, and that this autoimmunity initiates and/or amplifies the degeneration of iris pigment epithelium and stromal atrophy. As a consequence, secondary structural changes in the anterior chamber, especially at the angle and trabecular meshwork, lead to increased intraocular pressure and eventual optic neuropathy.